An increase in the number of immunocompromised patients and the incidence of drug-resistant infections has created a significant challenge for the pharmaceutical industry in the area of antifungal therapeutics. Traditional antifungal drug discovery and development involves a one- target approach that takes seven to twelve years. As a result, the demand for new, more effective, less toxic, antifungals has outpaced their development. Acacia Biosciences, Inc. has developed proprietary technology for monitoring Saccharomyces cerevisiae gene expression on a genome-wide level. We propose to develop databases and assays that will accelerate the discovery of antifungal drugs by using our Genome Reporter Matrix. This approach has three distinct advantages over traditional drug discovery methods. First, our assay is easily adapted to any target irrespective of its function. Second, our genomic approach yields a large amount of biological information, concomitantly generating new hypotheses concerning fungal biology and the mechanism of action of drugs. Last, computerized comparison of Acacia's genetic-response profile database and chemical response profile database results in the rapid identification of potential lead compounds for any target. This phase I proposal will allow us to build a foundation for a program of antifungal drug discovery. PROPOSED COMMERCIAL APPLICATIONS: The development of highly adaptable assays for antifungal drugs acting against targets of known or unknown function would have high commercial value for drug development. We expect to develop and commercialize such assays using our genomic technology. These research tools will make antifungal drug discovery faster and more effective.